Vaccines and methods to treat lyme disease in dogs
View Patent ↗The instant invention provides an immunogenic composition comprising an antigenic fragment of OspA protein of Borrelia burgdorferi and a chimeric protein containing antigenic fragments of different phylotypes of OspC protein of Borrelia burgdorferi . Vaccines incorporating the immunogenic composition of the invention, as well as methods of preventing Lyme disease in dogs and/or protecting dogs from Lyme disease using the vaccines are also provided.
1. An immunogenic composition comprising:
A) a first protein comprising an amino acid sequence at least 95% identical to SEQ ID NO: 1; and
B) a second protein, comprising immunodominant epitopes of OspC phylotypes F and N; wherein said composition is useful for preventing or reducing the pathological effects of infection with Borrelia burgdorferi in a canine, wherein said second protein comprises
i) at least one of an amino acid sequence at least 95% identical to SEQ ID NO: 8 and an amino acid sequence at least 95% identical to SEQ ID NO: 9; and
ii) an amino acid sequence 95% identical to SEQ ID NO: 32.
2. The immunogenic composition of claim 1 , wherein the first protein comprises SEQ ID NO; 1.
3. The immunogenic composition of claim 1 , wherein the second protein further comprises:
a plurality of peptides at least 95% identical to immunodominant epitopes from loop 5 region (loop peptide) and alpha helix 5 region (helix peptide) of OspC phylotype I, H, C, M, and D.
4. The immunogenic composition of claim 3 wherein:
Loop peptide I is SEQ ID NO: 4;
Helix peptide I is SEQ ID NO: 5;
Loop peptide H is SEQ ID NO: 6;
Helix peptide H is SEQ ID NO: 7;
Loop peptide C is SEQ ID NO: 10;
Helix peptide C is SEQ ID NO: 11;
Loop peptide M is SEQ ID NO: 12;
Helix peptide M is SEQ ID NO: 13;
Loop peptide D is SEQ ID NO: 14;
Helix peptide D is SEQ ID NO: 15.
5. The immunogenic composition of claim 1 , wherein the amino acid sequence 95% identical to SEQ ID NO 32 is at the carboxy terminus of said second protein.
6. The immunogenic composition of claim 1 , wherein the second protein comprises, in N- to C-orientation, an I-construct, a H-construct, a N-construct, a C-construct, a M-construct, a D-construct.
7. The immunogenic composition of claim 1 , wherein the second protein further comprises a plurality of peptides 95% identical to immunodominant epitopes from loop 5 region (loop peptide) and alpha helix 5 region (helix peptide) of OspC phylotypes T, U, E.
8. , The immunogenic composition of claim 7 , wherein the second protein comprises, in N- to C-orientation, a T- construct, a U-construct, an E-construct.
9. The immunogenic composition of claim 1 , wherein the second protein further comprises a plurality of peptides 95% identical to immunodominant epitopes from loop 5 region (loop peptide) and alpha helix 5 region (helix peptide) of OspC phylotypes A, B, K.
10. The immunogenic composition of claim 9 , wherein the second protein comprises, in N- to C-orientation, an A-construct, a B-construct, a K-construct.
11. The immunogenic composition of claim 1 , wherein the second protein comprises, in N- to C-orientation, the T-construct, the U-construct, the E-construct, an A-construct, a B-construct, a K-construct.
12. The immunogenic composition of claim 11 , wherein the second protein comprises, in N- to C-orientation, the T-construct, the U-construct, the E-construct, the A-construct, the B-construct, the K-construct, an I-construct, an H-construct, an N-construct, a C-construct, an M-construct, a D-construct.
13. The immunogenic composition according to claim 1 , wherein the loop peptides and the helix peptide from each phylotype are adjacent to each other.
14. The immunogenic composition according to claim 3 , wherein the loop peptides and the helix peptides for each phylotype are arranged sequentially.
15. The immunogenic composition of claim 3 , wherein the loop peptide for each phylotype is upstream of the corresponding helix peptide for that phylotype.
16. The immunogenic composition according to claim 1 , wherein
a. the first protein is SEQ ID NO: 1; and
b. the second protein is SEQ ID NO: 30.
17. The immunogenic composition according to claim 1 , wherein
a. the first protein is SEQ ID NO: 1; and
b. the second protein is SEQ ID NO: 31.
18. The immunogenic composition of claim 1 further comprising at least one additional antigen preventing or reducing the pathological effects of infection with a microorganism that can cause disease in dogs.
19. The immunogenic composition of claim 18 , wherein said microorganism is selected from the group consisting of canine distemper (CD) virus, canine adenovirus type 2 (CAV-2), canine parainfluenza (CPI) virus, canine parvovirus (CPV), canine coronavirus (CCV), canine herpesvirus, and rabies virus.
20. A vaccine composition comprising the immunogenic composition according to claim 17 and an adjuvant.
21. The vaccine composition of claim 20 , wherein the adjuvant is selected from the group consisting of mineral salts, surface-active agents and microparticles, bacterial products, cytokines and hormones, carriers, oil-in-water emulsions and water-in-oil emulsions.
22. A method of preventing or reducing the pathological effects of infection with Borrelia burgdorferi in a canine comprising administering the canine in need thereof an immunologically effective dose of the vaccine composition according to any one of claims 20 and 21 .
23. A method of preventing or reducing the pathological effects of infection with Borrelia burgdorferi in a canine comprising administering the canine in need thereof an immunologically effective dose of the immunogenic composition according to any one of claims 1, 2, 3, 4, 5, 17.